Patterns of Failure After Definitive Trimodality Therapy for Muscle-Invasive Bladder Cancer
Nikhil V Kotha1, Abhishek Kumar2, Paul Riviere3
1Department of Radiation Oncology, Stanford University. Palo Alto, CA; Department of Radiation Medicine and Applied Sciences, University of California San Diego. La Jolla, CA; Veterans Affairs San Diego Healthcare System. San Diego, CA.
Background:
Real-world outcomes, especially patterns of failure, are limited for patients with muscle-invasive bladder cancer (MIBC) treated with trimodality therapy (TMT). We aim to evaluate patterns of failure after TMT for MIBC in a typical heterogeneous population.
Methods:
In the national Veterans Affairs database, patients with urothelial histology, MIBC (T2-4a/N0-3/M0) who underwent definitive intent TMT between 2000-2018. Successful TMT was defined as ≥ 50% definitive radiation dose and ≥ 1 cycle chemotherapy. Endpoints of any recurrence, metastatic (nonbladder) recurrence (MR), and local (bladder) recurrence (LR) evaluated in multivariable Fine-Gray models. Times to recurrence calculated from radiation start date.
Results:
In 347 patients with MIBC treated with TMT, 65% of patients were deemed ineligible for surgery while 35% were surgically eligible but elected for TMT. Median follow-up time was 77 months. Median overall survival was 32.4 months (95% CI: 28.2-36.7). 154 (44%) patients had no recurrence. 130 (37%) patients developed MR, median time 9.9 months. 117 (34%) patients developed LR, median time 8.7 months. In multivariable models, lymph node positive (LN+) disease (HR:3.31, 95% CI: 1.45-7.55, P < .01) and pretreatment hydronephrosis (HR:1.62, 95% CI:1.11-2.36, P = .01) were associated with higher rates of MR. No patient, tumor, or treatment variables were associated with LR.
Conclusions:
Across a multi-institutional and heterogeneous population, TMT is an effective treatment for many real-world patients with MIBC. However, a notable proportion of patients develop MR and/or LR which emphasizes the need for post-treatment surveillance and improved treatment pathways. Identified high risk features (LN+ disease, pretreatment hydronephrosis) and other markers should be further investigated to delineate the patients at high risk of TMT failure who therefore may potentially benefit from augmented treatment, such as additional systemic therapy.
Insights
Trimodality therapy (TMT) is effective for muscle-invasive bladder cancer (MIBC), but some patients experience recurrence. Lymph node positive disease and hydronephrosis predict metastatic recurrence, highlighting the need for improved surveillance and treatment strategies.
Area of Science:
- Urology
- Oncology
- Medical Outcomes
Background:
- Real-world data on muscle-invasive bladder cancer (MIBC) treatment patterns, particularly failure modes after trimodality therapy (TMT), are limited.
- Understanding these outcomes in a diverse patient population is crucial for optimizing care.
Purpose of the Study:
- To evaluate the patterns of failure, including local recurrence (LR) and metastatic recurrence (MR), in patients with MIBC treated with TMT.
- To identify risk factors associated with recurrence after TMT.
Main Methods:
- Retrospective analysis of 347 patients with MIBC (T2-4a/N0-3/M0) treated with definitive TMT between 2000-2018 in the Veterans Affairs database.
- Successful TMT defined by radiation dose and chemotherapy cycles. Time-to-recurrence evaluated using multivariable Fine-Gray models.
- Endpoints included any recurrence, MR, and LR, with time calculated from radiation start.
Main Results:
- 44% of patients experienced no recurrence; 37% developed MR (median time 9.9 months); 34% developed LR (median time 8.7 months).
- Lymph node positive (LN+) disease and pretreatment hydronephrosis were significantly associated with higher rates of MR (P < .01 and P = .01, respectively).
- No patient, tumor, or treatment variables were associated with LR.
Conclusions:
- TMT is an effective treatment for many real-world MIBC patients, but a significant proportion experience recurrence.
- The study identifies LN+ disease and pretreatment hydronephrosis as key predictors of MR, suggesting a need for tailored surveillance.
- Findings emphasize the importance of post-treatment monitoring and warrant further investigation into augmented treatment strategies for high-risk patients.
